Triethylamine → 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine

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Reaction Conditions

Reaction Steps

and (b) A mixture of 1-ethyl-6-nitro-4-chloro-1H-pyrazolo[3,4-b]quinoline (2.7 g, 17.8 mmol), triethylamine (3 ml, 0.02 mol), DMSO (15 ml) and 3-hydroxycyclohexylmethylamine (4.97 g, 18 mmol) is heated at 110° C. overnight. The reaction mixture is poured into ice water (200 ml)/NH4OH (10 ml) and the solid which forms is collected by filtration. The filtrate is then extracted with CH2Cl2 (2×100 ml). The solid is stirred and sonicated with CH2Cl2 (2×200 ml), and any solids which did not go into solution are collected by filtration. All of the above CH2Cl2 filtrates and extracts are combined, washed with water and evaporated. The residue is slurried with ethyl acetate (10-15 ml)/ether (20 ml) and a red colored solid is collected by filtration and washed with ether. The solid is purified by column chromatography (2×) on silica gel (note that the solid is preloaded onto 50-100 g of silica gel) eluting with 40% THF/cyclohexane and each of the diastereomers which is isolated is dissolved in hot THF, filtered and the solvent is evaporated. Each of the residues is slurried with ethanol (5 ml), filtered and dried to afford 0.69 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine (the RS,SR diastereomer which is labelled as Example 36(a)), m.p. 236°-238° C. and 2.23 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine (the RR,SS diastereomer which is labelled as Example 36(b)), m.p. 247°-248° C.

Provenance & Evidence